nampt-in-1

Nampt-IN-1 (LSN3154567) (LSN3154567) is a potent and selective NAMPT inhibitor. Nampt-IN-1 inhibits purified NAMPT with an IC50 of 3.1 nM.

PARP/NAMPT-IN-1 (Compound 13j) is a dual-target inhibitor of PARP and NAMPT, with IC50 values of 0.8 nM for PARP1 and 18 nM for NAMPT. It suppresses breast cancer cell proliferation and migration, inducing apoptosis. PARP/NAMPT-IN-1 is applicable for research on triple-negative breast cancer.

Mutant IDH1/NAMPT-IN-1 (Compound 23h) is a dual inhibitor of mutant isocitrate dehydrogenase 1 (mutantIDH1) with an IC50 of 14.93 nM, and nicotinamide phosphoribosyltransferase (NAMPT) with an IC50 of 12.56 nM. This compound can induce apoptosis and effectively crosses the blood-brain barrier.

BRD4/NAMPT-IN-1 (Compound A2) exhibits strong inhibitory effects on NAMPT and BRD4, with IC50 values of 35 nM (NAMPT) and 58 nM (BRD4). This compound significantly suppresses the growth and migration of liver cancer cells while promoting apoptosis. Additionally, BRD4/NAMPT-IN-1 demonstrates potent anticancer activity in HCCLM3 xenograft mouse models without noticeable toxicity.

PD-L1/Nampt-IN-1 is an orally active inhibitor that targets both PD-L1 and NAMPT (nicotinamide phosphoribosyltransferase), with IC50 values of 63 nM and 582 nM, respectively. It exhibits cross-species affinity, with KD values of 52.6 nM for hPD-L1 and 49.1 nM for mPD-L1. This compound effectively suppresses tumor growth by activating the tumor immune microenvironment and is applicable in melanoma research.

CAIX/XII/NAMPT-IN-1 is a triple inhibitor targeting carbonic anhydrase IX/XII (CAIX/XII) and nicotinamide phosphoribosyltransferase (NAMPT), with a Ki of 78.1 nM for hCA IX, a Ki of 64.4 nM for hCA XII, and an IC50 of 168 nM for hNAMPT. It induces apoptosis, promotes the accumulation of reactive oxygen species (ROS), inhibits the ERK/AKT signaling pathway, blocks DNA synthesis, and disrupts mitochondrial function. CAIX/XII/NAMPT-IN-1 exhibits antiproliferative effects on various cancer cells under both normoxic and hypoxic conditions. This compound is useful for cancer research, including studies on renal cancer, glioblastoma, and colorectal cancer.

HDAC/NAMPT-IN-1 (compound 39h) simultaneously inhibits HDAC and NAMPT, exhibiting IC 50 values ranging from 0.72 to 37081 nM for HDAC and 1618 nM for NAMPT [1].

Nampt-IN-13 TFA is a NAMPT inhibitor (patent WO2021013693A1) suitable for synthesising antibody-drug conjugates (ADCs).

Nampt-IN-10 trihydrochloride (Compound 4) is a Nicotinamide Phosphoribosyltransferase (NAMPT) inhibitor exhibiting cellular potency against A2780 and CORL23 cell lines, with IC50 values of 5 nM and 19 nM, respectively. It holds potential as a novel non-antimitotic payload for antibody-drug conjugate (ADC) [1].

Nampt-IN-13 (example 58m) is an NAMPT inhibitor used in the synthesis of antibody-drug conjugates (ADCs).

Nampt-IN-15 (Example 3) is a Nampt inhibitor that exhibits cytotoxic effects on various cell lines, including BxPC-3, HepG2, L540cy, and MOLM-13. The respective IC50 values for these cell lines are 38.5 nM, 8 nM, 8.5 nM, and 7 nM.

Nampt-IN-16 (Compound 9a) is an orally active NAMPT inhibitor with an IC50 of 0.15 μM. It reduces intracellular NAD+ and ATP levels. Nampt-IN-16 inhibits the proliferation, migration, and invasion of gastric cancer cells, induces cell cycle arrest and apoptosis, and alters cellular metabolism. This compound is applicable for research in tumors such as gastric cancer.

Nampt-IN-10 (Compound 4) is a potent inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). It exhibits nanomolar inhibitory activity against cell lines such as MDA-MB453, NCI-N87, and NCI-H526. Nampt-IN-10 can serve as an ADC payload, with ADCs constructed around it showing significant antitumor activity.

Nampt-IN-17 is an orally active selective NAMPT inhibitor with an IC50 of 17 nM and a Ki of 25.9 nM for human NAMPT. It depletes intracellular NAD+ and ATP, disrupts mitochondrial membrane potential, inhibits cell proliferation, self-renewal, invasion, and migration, and induces cell cycle arrest and apoptosis (apoptosis). Nampt-IN-17 exhibits selective activity against NAPRT-deficient gastric cancer cells and is suitable for research related to NAPRT-deficient gastric cancer.

Nampt-IN-18 (Compound Q24) is an orally active NAMPT inhibitor with an IC50 of 8.0 nM against hNAMPT. It suppresses NAMPT enzymatic activity, inhibits DNA synthesis, and induces apoptosis. Additionally, Nampt-IN-18 exhibits anticancer properties against gastric and colorectal cancers and is useful in gastrointestinal cancer research.

Nampt-IN-10 TFA (compound 4) is a phosphoribosyltransferase (NAMPT) inhibitor with cellular efficacy against A2780 (IC50: 5 nM) and CORL23 (IC50: 19 nM), and can be used as a non-antimitotic payload for ADCs.

Nampt-IN-12 (compound 9), a derivative of N-Pyridinylthiophene carboxamid, exhibits activity against peripheral nerve sheath cancer cells. It is metabolized by the enzymes NAMPT and NMNAT1 within the NAD salvage pathway into an adenine dinucleotide (AD) derivative, an analog of NAD that can inhibit inosine monophosphate dehydrogenase (IMPDH), leading to the accumulation of inosine monophosphate (IMP) within the cells. Nampt-IN-12's effective blood-brain barrier permeability makes it suitable for research into cancers of the central and peripheral nervous system.

Nampt-IN-14 (example 3) is an effective NAMPT inhibitor with an IC50 of 0.2 nM, suited for use in the synthesis of antibody-drug conjugates (ADCs).

PDEδ/NAMPT IN-1 (Compound 17d) is a dual inhibitor targeting phosphodiesterase 6 (PDE6) with a dissociation constant (KD) of 0.410 nM and nicotinamide phosphoribosyltransferase (NAMPT) with an inhibitory concentration (IC50) of 2.21 nM. It disrupts KRAS-related signaling by inhibiting NAMPT's role in the synthesis of nicotinamide adenine dinucleotide (NAD+), consequently inducing apoptosis in pancreatic cancer cells with KRAS mutations. This compound holds potential for research in KRAS-mutant pancreatic cancer.

NAMPT inhibitor-linker 1, a drug-linker conjugate for ADC, integrates an NAMPT inhibitor (as a payload) with a linker. In the formulation of ADC-3, it pairs with an anti-c-Kit monoclonal antibody, demonstrating strong efficacy against c-Kit expressing cell lines, specifically GIST-T1 and NCI-H526, where it exhibits IC50 values of <3 pM and 9 pM, respectively.

LZFPN-90 (LZ90) is a dual-target compound aimed at NAMPT and PD-L1. It inhibits the interaction between PD-1/PD-L1 and NAMPT activity. LZFPN-90 suppresses cell growth in a NAMPT-dependent manner, blocking the cell cycle and subsequently inducing apoptosis. Additionally, LZFPN-90 exhibits target-dependent antitumor activity, impacting metabolic processes and the immune system.

7-Bromoheptanoic acid is a building block.1,2It has been used in the synthesis of azide-based nicotinamide phosphoribosyltransferase (Nampt) inhibitors with anticancer activity and SAHA derivatives that inhibit histone deacetylases (HDACs). 1.Colombano, G., Travelli, C., Galli, U., et al.A novel potent nicotinamide phosphoribosyltransferase inhibitor synthesized via click chemistryJ. Med. Chem.53(2)616-623(2010) 2.Suzuki, T., Nagano, Y., Kouketsu, A., et al.Novel inhibitors of human histone deacetylases: Design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamatesJ. Med. Chem.48(4)1019-1032(2005)

KPT9274 (PAK4-IN-1) is a non-competitive dual inhibitor of PAK4 and NAMPT(IC50= ~120 nM). It is an orally bioavailable small molecule.

NAT is a nicotinamide phosphoribosyltransferase (NAMPT) activator that increases intracellular NAD levels and induces subsequent metabolic and transcriptional reprogramming. It exhibits neuroprotective effects in a chemotherapy-induced peripheral neuropathy (CIPN) mouse model and may be employed in studies of neurodegenerative diseases or conditions associated with reduced NAD levels.